Degenerative changes and calcification of articular cartilages both increase with aging but suspected cause and effect relationships between the calcifications and any measures of cartilage degenerative change have not previously been examined. We suspect that a) cartilage calcification is a result of a biochemical change that occurs with aging and b) the calcification although not the sole cause of osteoarthritis may contribute to the severity of osteoarthritis by the mechanical effect of calcium pyrophosphate (CPPD) and apatite crystals on cartilage matrix and/or by induction of a low grade inflammation induced by these crystals leading to release of enzymes that damage cartilage. We propose to sequentially study patients with osteoarthritis to correlate the frequency of calcium crystals with age, severity of degenerative arthritis and evidence of inflammation assessed clinically and by analysis of synovial fluid. We propose that crystal presence will increase with age and will correlate with greater though still low-grade inflammation and more severe osteoarthritis. We will also examine knee articular cartilages on all autopsies at the Phila. VA Hospital by transmission electron microscopy, electron probe energy dispersive elemental analysis and histochemistry to systematically correlate CPPD and apatite calcifications for the first time with age, cartilage degeneration and inflammation or proliferation as seen in the synovial membrane. We will search for earliest sites and smallest crystal deposits and test histochemical and a newer (Spurr's) tissue handling technique allowing more rapid crystal identification of potential clinical diagnostic usefulness. These morphologic studies will give us important clues to roles of aging related changes in pathogenesis of osteoarthritis, an important cause of disability with aging. Extensions of the morphologic studies with biomechanical and biochemical correlations will be planned to hope to later intervene in correcting some of the aging changes leading to cartilage degeneration.